Frog metamorphosis is an excellent model system to understand the mechanisms of postembryonic developmental processes. The changes that occur during metamorphosis are controlled by thyroid hormone (TH), and related changes occur in all vertebrates. Thyroid hormone receptors (TRs) are presumed to mediate the effects of TH on metamorphosis and understanding their role will provide important information about the mechanisms of post-embryonic development. Research experiments in this proposal take advantage of the simple but well-characterized metamorphic process, the remodeling of the frog intestine in vivo to investigate the roles of TRs in regulating cell fate, i.e., cell proliferation vs. apoptosis, during development. The experimental approaches involve the application of the recently developed transgenic methodologies and the use of a battery of microscopic, molecular and cellular analysis techniques. Transgenesis will allow me to alter expression levels or the function of TRs in living tadpoles, and the resulting effects on morphological transformation and gene activity during intestinal metamorphosis will be examined. The experiments proposed herein will directly demonstrate whether TRs mediate TH- induced metamorphic events in vivo in an organ and/or cell autonomous fashion. In addition, these experiments directly address the hypothesis that TRs play dual functions during vertebrate development, i.e., repressing TH-regulated genes in the absence of TH and activating them in the presence of TH.